rs104895004

Variant names:

• chr11-94418192-C-A
• rs104895004
• NM_005591.4:c.*1933G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-94418192-C-A
• chr11-94418192-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005591.4(MRE11):​c.*1933G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 232,922 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (1 hom.)
• Consequence: MRE11 NM_005591.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 O:1
• Conservation: PhyloP100: -0.246
• Publications: 3 publications found

Genes affected

MRE11 (HGNC:7230): (MRE11 homolog, double strand break repair nuclease) This gene encodes a nuclear protein involved in homologous recombination, telomere length maintenance, and DNA double-strand break repair. By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 homolog; this complex is required for nonhomologous joining of DNA ends and possesses increased single-stranded DNA endonuclease and 3' to 5' exonuclease activities. In conjunction with a DNA ligase, this protein promotes the joining of noncomplementary ends in vitro using short homologies near the ends of the DNA fragments. This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MRE11 Gene-Disease associations (from GenCC):

• ataxia-telangiectasia-like disorder 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• prostate cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005591.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRE11	NM_005591.4	MANE Select	c.*1933G>T		3_prime_UTR	Exon 20 of 20	NP_005582.1	P49959-1
	MRE11	NM_001440460.1		c.*1933G>T		3_prime_UTR	Exon 21 of 21	NP_001427389.1
	MRE11	NM_001440461.1		c.*1933G>T		3_prime_UTR	Exon 21 of 21	NP_001427390.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRE11	ENST00000323929.8	TSL:1 MANE Select	c.*1933G>T		3_prime_UTR	Exon 20 of 20	ENSP00000325863.4	P49959-1
	MRE11	ENST00000856310.1		c.*1933G>T		3_prime_UTR	Exon 20 of 20	ENSP00000526369.1
	MRE11	ENST00000856311.1		c.*1933G>T		3_prime_UTR	Exon 20 of 20	ENSP00000526370.1

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 377 AN: 152044 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000918

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00623

GnomAD4 exome AF: 0.00322 AC: 260 AN: 80760 Hom.: 1 Cov.: 0 AF XY: 0.00337 AC XY: 125 AN XY: 37112

African (AFR) AF: 0.000515 AC: 2 AN: 3884

American (AMR) AF: 0.00282 AC: 7 AN: 2486

Ashkenazi Jewish (ASJ) AF: 0.00117 AC: 6 AN: 5118

East Asian (EAS) AF: 0.00 AC: 0 AN: 11332

South Asian (SAS) AF: 0.00 AC: 0 AN: 698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 58

Middle Eastern (MID) AF: 0.00203 AC: 1 AN: 492

European-Non Finnish (NFE) AF: 0.00433 AC: 216 AN: 49936

Other (OTH) AF: 0.00414 AC: 28 AN: 6756

GnomAD4 genome AF: 0.00247 AC: 376 AN: 152162 Hom.: 1 Cov.: 32 AF XY: 0.00208 AC XY: 155 AN XY: 74400

African (AFR) AF: 0.000915 AC: 38 AN: 41514

American (AMR) AF: 0.00307 AC: 47 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.000567 AC: 6 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00379 AC: 258 AN: 68002

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.00301

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Ataxia-telangiectasia-like disorder 1 (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.58
PhyloP100		-0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs104895004; hg19: chr11-94151358;